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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2021年03期

页码:

283-287

栏目:

论著

出版日期:

2021-06-20

文章信息/Info

Title:

Role of peripheral cytokines in lung cancer pathological typing and prognosis

作者:

许琼¹; 马硝惟²; 刘斌¹; 蒋捍东¹; 吴学玲¹

201112 上海,上海交通大学医学院附属仁济医院呼吸科¹、检验科²

Author(s):

Xu Qiong¹;  Ma Xiaowei²;  Liu Bin¹;  Jiang Handong¹;  Wu Xueling¹.

¹Department of Respiratory; ²Clinical laboratory, Shanghai Jiaotong University School of Medicine, Renji Hospital, Shanghai 201112, China

关键词:

支气管肺癌;  白介素6;  病理分型;  预后

Keywords:

Bronchogenic carcinoma;  Interleukin 6;  Pathological typing;  Prognosis

分类号:

R563

DOI:

10.3877/cma.j.issn.1674-6902.2021.03.004

摘要:

目的 探讨细胞因子在肺癌不同病理类型和预后判断中的意义。方法 收集就诊于上海交通大学附属仁济医院的127例肺癌患者以及11例支气管哮喘、68例社区获得性肺炎患者的临床数据,包括病理类型、生存时间、临床分期、年龄等,同时收集这些患者多次入院病程中外周血细胞因子和肺癌相关肿瘤指标的实验室检查资料。统计分析细胞因子在肺癌、支气管哮喘和社区获得性肺炎中的表达差异。筛选出肺癌患者中升高的细胞因子,并统计分析它与肺癌分期、病理类型及预后的相关性。结果 IL-6在肺癌患者中的水平明显高于支气管哮喘和社区获得性肺炎组(P<0.001),而其它的细胞因子在这三种疾病中的表达无明显差异。IL-6在肺鳞癌患者中升高最为明显; IL-6水平的高低与临床TNM分期相关,在Ⅲ、Ⅳ期肺癌患者中最高(P<0.05)。在肺癌的死亡患者中,血IL-6的水平随疾病的进展逐步升高,相关回归分析具有统计学差异(P<0.01)。生存分析显示IL-6高水平组的生存时间短于IL-6低水平组,风险比为3.04(P<0.05)。结论 IL-6与肺癌患者病情进展及预后相关。

Abstract:

Objective To investigate the effectiveness of cytokines as pathological and prognostic markers for lung cancer. Methods Peripheral levels of cytokines and lung cancer related tumor markers during multiple hospitalization, as well as clinical data, including pathological type, survival time, clinical stage and age, were collected in a retrospective cohort with 127 lung cancer patients, 11 asthma and 68 pneumonia patients. All patients were admitted to Renji hospital, Shanghai Jiao Tong University School of Medicine. To identify new markers for lung cancer diagnostics, levels of cytokines were compared between lung cancer, asthma and pneumonia patients with statistical tests. The dynamics of significant cytokines were further evaluated among disease stages and during disease progression. Results The cytokine IL-6 levels were significantly higher in lung cancer compared to that in asthma and pneumonia patients(P<0.001). However, the level of other cytokines were not statistically different among these three groups. Furthur analysis showed that IL-6 levels were related to pathological type with highest level in squamous lung cancer. IL-6 levels were also associated with TNM stage, and were higher in Ⅲ-Ⅳ stages(P<0.05). It was significantly increased with disease progression in patients who died of lung cancer(P<0.01). For individuals with high levels of IL-6, poorer overall survival was observed compared to those with lower levels of this cytokine(hazard ratio=3.04, P<0.05). Conclusion Peripheral IL-6 level is an effective marker for lung cancer progression and prognostic analysis.

参考文献/References:

1 钱桂生. 肺癌不同病理类型发病率的变化情况及其原因[J/CD]. 中华肺部疾病杂志(电子版), 2011, 4(1): 1-5.
2 WHO. Available online at: http://gco.iarc.fr/today/fact-sheets-populations? population=160&sex=0#collapse1. Global Cancer Observatory Population Fact Sheets, accessed April, 2021.
3 Jiang ZF, Wang M, Xu JL. Thymidine kinase 1 combined with CEA, CYFRA21-1 and NSE improved its diagnostic value for lung cancer[J]. Life Sci, 2018, 194: 1-6.
4 Zimmerman R, Wahren B, Edsmyr F. Assessment of serial CEA determinations in urine of patients with bladder carcinoma[J]. Cancer, 1980, 46(8): 1802-1809.
5 Zhao M, Liu Y, Liu R, et al. Upregulation of IL-11, an IL-6 family cytokine, promotes tumor progression and correlates with poor prognosis in non-small cell lung cancer[J]. Cell Physiol Biochem, 2018, 45(6): 2213-2224.
6 Smyth MJ, Cretney E, Kershaw MH, et al. Cytokines in cancer immunity and immunotherapy[J]. Immunol Rev, 2004, 202: 275-293.
7 Tang H, Bai Y, Shen W, et al. Clinical significance of combined detection of interleukin-6 and tumour markers in lung cancer[J]. Autoimmunity, 2018, 51(4): 191-198.
8 Naqash AR, Yang LV, Sanderlin EJ, et al. Interleukin-6 as one of the potential mediators of immune-related adverse events in non-small cell lung cancer patients treated with immune checkpoint blockade: evidence from a case report[J]. Acta Oncol, 2018, 57(5): 705-708.
9 Pinargote-Celorio H, Miralles G, Cano M, et al. Cytokine levels predict 30-day mortality in octogenarians and nonagenarians with community-acquired pneumonia: a retrospective observational study[J]. Eur J Clin Microbiol Infect Dis, 2020, 39(2): 299-307.
10 Mendez R, Menendez R, Cilloniz C, et al. Initial inflammatory profile in community-acquired pneumonia depends on time since onset of symptoms[J]. Am J Respir Crit Care Med, 2018, 198(3): 370-378.
11 Bazan-Socha S, Mastalerz L, Cybulska A, et al. Prothrombotic state in asthma is related to increased levels of inflammatory cytokines, IL-6 and TNFalpha, in peripheral blood[J]. Inflammation, 2017, 40(4): 1225-1235.
12 Kumari N, Dwarakanath BS, Das A, et al. Role of interleukin-6 in cancer progression and therapeutic resistance[J]. Tumour Biol, 2016, 37(9): 11553-11572.
13 Chu Y, Wang Y, Peng W, et al. STAT3 activation by IL-6 from adipose-derived stem cells promotes endometrial carcinoma proliferation and metastasis[J]. Biochem Biophys Res Commun, 2018, 500(3): 626-631.
14 Knupfer H, Preiss R. Significance of interleukin-6(IL-6)in breast cancer(review)[J]. Breast Cancer Res Treat, 2007, 102(2): 129-135.
15 Lin Y, He Z, Ye J, et al. Progress in understanding the IL-6/STAT3 Pathway in Colorectal Cancer[J]. Onco Targets Ther, 2020, 13: 13023-13032.
16 Kucera R, Topolcan O, Treskova I, et al. Evaluation of IL-2, IL-6, IL-8 and IL-10 in malignant melanoma diagnostics[J]. Anticancer Res, 2015, 35(6): 3537-3541.
17 Pan YW, Zhou ZG, Wang M, et al. Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis[J]. Genet Mol Res, 2016, 15(4). doi: 10.4238/gmr15048949.
18 Chang CH, Hsiao CF, Yeh YM, et al. Circulating interleukin-6 level is a prognostic marker for survival in advanced nonsmall cell lung cancer patients treated with chemotherapy[J]. Int J Cancer, 2013, 132(9): 1977-1985.
19 Huang X, Xiao S, Zhu X, et al. miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL-6-STAT3 signaling[J]. Cell Death Dis, 2020, 11(9): 785.
20 Hong DS, Angelo LS, Kurzrock R. Interleukin-6 and its receptor in cancer: implications for translational therapeutics[J]. Cancer, 2007, 110(9): 1911-1928.
21 Lederle W, Depner S, Schnur S, et al. IL-6 promotes malignant growth of skin SCCs by regulating a network of autocrine and paracrine cytokines[J]. Int J Cancer, 2011, 128(12): 2803-2814.
22 Fisher DT, Appenheimer MM, Evans SS. The two faces of IL-6 in the tumor microenvironment [J]. Semin Immunol, 2014, 26(1): 38-47.
23 Loeb LA, Ernster VL, Warner KE, et al. Smoking and lung cancer: an overview[J]. Cancer Res, 1984, 44(12 Pt 1): 5940-5958.
24 Hackshaw AK, Law MR, Wald NJ. The accumulated evidence on lung cancer and environmental tobacco smoke[J]. BMJ, 1997, 315(7114): 980-988.
25 Chen PH, Chang H, Chang JT, et al. Aryl hydrocarbon receptor in association with RelA modulates IL-6 expression in non-smoking lung cancer[J]. Oncogene, 2012, 31(20): 2555-2565.
26 Koo JB, Han JS. Cigarette smoke extract-induced interleukin-6 expression is regulated by phospholipase D1 in human bronchial epithelial cells[J]. J Toxicol Sci, 2016, 41(1): 77-89.
27 Xie C, Zhu J, Jiang Y, et al. Sulforaphane inhibits the acquisition of tobacco smoke-induced lung cancer stem cell-like properties via the IL-6/DeltaNp63alpha/Notch Axis[J]. Theranostics, 2019, 9(16): 4827-4840.
28 Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer[J]. N Engl J Med, 2018, 378(22): 2078-2092.
29 Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer(CASPIAN): a randomised, controlled, open-label, phase 3 trial[J]. Lancet, 2019, 394(10212): 1929-1939.
30 Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer[J]. N Engl J Med, 2015, 372(21): 2018-2028.

备注/Memo

备注/Memo:

基金项目: 上海交大医学院附属仁济医院临床创新课题(2019NYLYCP0103)
通信作者: 吴学玲, Email: wuxueling@renji.com

常用功能

更新日期/Last Update: 2021-06-20